BACKGROUND Cancer cells always develop ways to resist and evade chemotherapy. To overcome this obstacle, herein, we introduce a programmatic release drug delivery system that imparts avoiding drug efflux and nuclear transport in synchrony via a simple nanostructured drug strategy. RESULTS The programmatic liposome-based nanostructured drugs (LNSD) contained two modules: doxorubicin (DOX) loaded into tetrahedral DNA (TD, ~ 10 nm) to form small nanostructured DOX, and the nanostructured DOX was encapsulated into the pH-sensitive liposomes. In the in vitro and in vivo studies, LNSD shows multiple benefits for drug resistance tumor treatment: (1) not only enhanced the cellular DOX uptake, but also maintained DOX concentration in an optimum level in resistant tumor cells via nanostructure induced anti-efflux effect; (2) small nanostructured DOX efficiently entered into cell nuclear via size depended nuclear-transport for enhanced treatment; (3) improved the pharmacokinetics and biodistribution via reducing DOX leakage during circulation. CONCLUSIONS The system developed in this study has the potential to provide new therapies for drug-resistant tumor.

中文翻译：

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基于超小纳米结构药物的pH敏感脂质体，可有效治疗耐药性肿瘤。

背景技术癌细胞总是开发出抵抗和逃避化学疗法的方法。为了克服这一障碍，在这里，我们介绍了一种程序释放药物输送系统，该系统通过简单的纳米结构药物策略同步避免药物外排和核转运。结果基于程序脂质体的纳米结构药物（LNSD）包含两个模块：阿霉素（DOX）加载到四面体DNA（TD，〜10 nm）中以形成小的纳米结构DOX，纳米结构DOX封装在pH敏感脂质体中。在体外和体内研究中，LNSD显示出对耐药性肿瘤治疗的多种益处：（1）不仅通过纳米结构诱导的抗外排效应，还增强了细胞对DOX的吸收，而且还使耐药性肿瘤细胞中的DOX浓度保持在最佳水平。 ; （2）小型纳米结构DOX通过大小依赖的核转运有效地进入细胞核，以进行增强处理；（3）通过减少循环过程中DOX的泄漏改善了药代动力学和生物分布。结论本研究开发的系统具有为耐药性肿瘤提供新疗法的潜力。